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Mauricio Reginato

Mauricio Reginato, PhD

Professor and Chair; Director, Graduate Program in Cancer Biology


Department: Biochemistry & Molecular Biology

Education

  • Postdoctoral Fellow, Harvard Medical School
  • PhD - Pharmacology, University of Pennsylvania
  • BS – Biology, Penn State University

Awards & Honors

  • Outstanding Mentor of the Year Award for the STAR Undergraduate Scholars, Drexel University (2023)
  • Julian Marsh Faculty Scholar Award, Drexel University College of Medicine (2021)
  • Elias Abrutyn Mentoring Award, Drexel University College of Medicine (2018)
  • Faculty Mentoring Award, MS Research Intensive Programs, Graduate Student Association, Drexel University College of Medicine (2016)
  • Young Investigator Award, Drexel University College of Medicine (2010)
  • Professional Enrichment and Growth Award, Drexel University College of Medicine (2010)

Memberships / Professional Affiliations

  • American Association of Cancer Research
  • American Society of Cell Biology
  • American Society for Biochemistry and Molecular Biology

Dr. Reginato is a professor and chair of the Department of Biochemistry & Molecular Biology, and director of the Graduate Program in Cancer Biology at Drexel University College of Medicine. Dr. Reginato also serves as program leader of the Translational Cellular Oncology Program at the Sidney Kimmel Cancer Center Research Consortium with Drexel University.

Research Overview

Research Interests

Molecular mechanisms regulating breast cancer growth and metastasis and understanding interplay between signaling and metabolic pathways to identify novel cancer therapies.

Research

Our lab is interested in understanding altered signaling pathways that lead to cancer initiation and progression and metastasis. Identifying and understanding these pathways will lead to development of novel therapies. Our lab is interested in understanding how signaling pathways regulate metabolic reprograming in cancer cells.

We are particularly interested in breast cancer. Every year approximately 200,000 new cases of breast cancer are diagnosed, and 40,000 women are expected to die from this disease in the U.S. alone. Our labs long-term goal is to identify novel therapeutic targets for treatment of breast cancer. We are trying to understand alterations in cellular signaling pathways between normal and cancer cells and exploit these differences for possible therapeutic gain.

Our lab has two major areas of interest:

1. Our lab is interested in understanding how oncogenes alter metabolic reprogramming in cancer cell. Tumor cells take up ten times more glucose then normal cells and switch to glycolysis to meet energy needs. Our lab was the first to show that a nutrient-sensing pathway that regulates sugar-based protein modification, called O-GlcNAcylation, is highly elevated in cancer. Our lab has shown that reducing O-GlcNAcylation in breast and prostate cancer cells inhibits growth, invasion and metastasis thus targeting the enzyme that regulates O-GlcNAcylation, O-GlcNAc transferase, may provide novel way of to treat cancers. We are currently investigating how O-GlcNAcylation regulates oncogenic signaling pathways using in vitro and in vivo breast cancer models. In addition, we are analyzing how cancer cells alter the O-GlcNAcome.

Targeting OGT levels in breast cancer cells blocks growth and invasion in 3D organoid culture.

3D Organoids: MDA-MB-231

Targeting OGT levels in breast cancer cells blocks growth and invasion in 3D organoid culture. Human breast cancer cells (MDA-MB-231) expressing control or OGT RNAi were cultured in three-dimensional (3D) culture. Organoids were imaged after eight days in culture by light (top) or confocal microscopy with indicated antibodies (bottom) (from Caldwell, et al., Oncogene 2010)

2. Breast cancer brain metastases remains incurable as more than 80% of patients will die within a year which is usually due to intracranial disease progression. Our lab is also interested in understanding how breast cancer cells adapt to the brain environment to survive and grow. We have developed novel ex vivo cancer slice model to quickly identify pathways and drugs that block cancer growth in the brain.

Breast Cancer Cells in the Brain Parenchyma

Ex vivo Brain Tumor Slice Model

Breast Cancer Cells in the Brain Parenchyma. Ex vivo mouse brain slices containing human breast cancer cells (green/blue) within brain parenchyma surrounded by activated astrocytes (red). Lab is using this model system to test new therapies for targeting breast cancer brain metastatic growth. Image provided by Lorela Ciraku & M. Reginato.

In the Media

“Drexel Team Identifies Drug-like Molecules That Show Early Success in Targeting Breast Cancer Brain Metastases”
Drexel News Blog (July 12, 2024)

“Awards Ceremony Celebrates Graduate School Class of 2024”
(May 14, 2024)

“Sidney Kimmel Cancer Center Research Consortium: Committed to Changing the Cancer Landscape in Philadelphia”
Pulse (Spring 2024)

"Starving Breast Cancer in the Brain"
EXEL - Drexel University Research Magazine (2023)

STAR Scholar Scales Real-World Learning Curve in Cancer Research
Drexel News (February 23, 2023)

2023 PA Breast Cancer Coalition Awards Dr. Reginato $100,000 Grant
College of Medicine Newsroom (May 2, 2023) - View Video on Vimeo

2021 Faculty Awards
Congratulations to Dr. Reginato, recipient of the 2021 Julian Marsh Faculty Scholar Award.

Additional articles...

2018 Faculty Awards
Congratulations to Dr. Reginato, recipient of the 2018 Elias Abrutyn Mentoring Award. See all 2018 faculty awardees.

2017 CURE Grant Awardees
(March 20, 2017)

"Teaming Up to Fight Brain Tumors"
College of Medicine Alumni Magazine (Fall/Winter 2016)

"Professors Receive Grants Through Statewide Refunds for Breast Cancer Research Campaign"
College of Medicine Newsroom (March 4, 2015)

"Cancer Groups Celebrate Pa. Program That Helps Taxpayers Donate to Research Programs"
CBS Philly (March 3, 2015)

"Drexel University researchers receive $100,000 through breast cancer research program"
Reading Eagle (January 27, 2015)

"Study Finds Novel Molecular Mechanism for Breast Cancer Cell Metabolism and Survival"
College of Medicine Newsroom (May 23, 2014)

"Third Annual Medical Student Research Day"
College of Medicine Newsroom (March 21, 2014)

"Cancer Discovery"
EXEL - Drexel University Research Magazine (2014)

"Study links cancer growth to sugar-based modification found naturally in the body"
News-Medical.Net (April 15, 2010)

Publications

Selected Publications

See all of Dr. Reginato's publications in ResearchGate.

“Fructose promotes liver cancer via microbial acetate-induced O-GlcNAcylation”
Esquea EM, Young RG, and Reginato MJ
Trends in Endocrinology & Metabolism, 2023 Dec 13:S1043-2760 (23)00247-3

“On a sugar high: Role of O-GlcNAcylation in cancer”
Le Minh, G, Esquea EM, Young RG, Huang, J, and Reginato MJ
Journal of Biological Chemistry, 2023 Oct 12, 105344

“Kruppel-like factor 8 regulates triple negative breast cancer stem cell-like activity”
Le Minh G, Esquea EM, Dhameliya TT, Merzy J, Lee MH, Ball LE, Reginato MJ
Frontiers in Oncolology. 2023 Apr 19;13:1141834

“Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity”
Le Minh G, Reginato MJ
Advanced Cancer Research. 2023;157:195-228

“O-GlcNAc Transferase Regulates Glioblastoma Acetate Metabolism via Regulation of CDK5-dependent ACSS2 phosphorylation”
Ciraku, L., Bacigalupa, Z. A., Ju, J., Moeller, R. A., Le Minh, G., Lee, R. H., Smith, M. D., Ferrer, C. M., Trefely, S., Izzo, L. T., Doan, M. T., Gocal, W. A., D'Agostino, L., Shi, W., Jackson, J. G., Katsetos, C. D., Wellen, K. E., Snyder, N. W., and Reginato, M. J.
Oncogene 2022 Apr;41(14):2122-2136

“O-GlcNAcylation regulation of cellular signaling in cancer”
Ciraku, L., Esquea, Reginato, M. J.
Cellular Signaling 2022 Nov 17;90

“An ex vivo brain slice model to study and target breast cancer brain metastatic tumor growth”
Ciraku, L., Moeller, R., Esquea, Gocal, W., Hartsough, E., Simone, N., Jackson, J., Reginato, M. J.
Journal Visualized Experiments 2021 Sep 22; (175)

“Role of hexosamine biosynthetic pathway on cancer stem cells: Connecting nutrient sensing to cancer cell plasticity”
Le Minh, G. and Reginato, M. J.
Comprehensive Pharmacology. 2021 Elsevier, Elizabeth Yeh (ed.)

“O-GlcNAc Transferase Regulates Cancer Stem-like Potential of Breast Cancer Cells”
Akella NM, Le Minh G, Ciraku L, Mukherjee A, Bacigalupa ZA, Mukhopadhyay D, Sodi VL, Reginato MJ
Molecular Cancer Research 2020 Apr;18(4):585-598

"Breast cancer brain metastasis response to radiation following microbubble oxygen delivery in a murine model"
Delaney L, Ciraku L, Oeffinger B, Wessner C, Liu J, Li J, Nam K, Forsberg F, Leeper D, O'Kane P, Wheatley M, Reginato MJ, Eisenbrey J
Journal of Ultrasound in Medicine 2019 Dec;38(12):3221-3228.

“Fueling the Fire: Emerging Role of the Hexosamine Biosynthetic Pathway in Cancer”
Akella NM, Ciraku L, and Reginato MJ
BMC Biology 2019 Jul 4;17(1):52

"O-GlcNAcylation: key regulator of glycolytic pathways"
Bacigalupa ZA, Bhadiadra C, and Reginato MJ
Journal of Bioenergetics and Biomembranes 2018 Jun;50(3):189-198

"Nutrient sensor O-GlcNAcylation controls cancer lipid metabolism via SREBP-1 regulation"
Sodi VL, Bacigalupa ZA, Ferrer CM, Lee J, Gocal W, Mukherjee D, Wellen KE, Ivan M, and Reginato MJ
Oncogene. 2018 Feb 15;37(7):924-934

"Metabolite profiling reveals the glutathione biosynthetic pathway as a therapeutic target in triple negative breast cancer"
Beatty A, Fink LS, Singh T, Strigun A, Peter E, Ferrer CM, Nicolas E, Cai KQ, Moran TP, Reginato MJ, Rennefahrt U, Peterson JR
Molecular Caner Therapeutics 2018 Jan;17(1):264-275

"The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells."
Segovia-Mendoza M, Díaz L, Prado-Garcia H, Reginato MJ, Larrea F and García-Becerra R
Am J Cancer Research. Jul 1 2017;7(7):1486-1500.

"Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis"
Li C, Li N, Liu X, Zhang EY, Sun Y, Masuda K, Li J, Sun J, Morrison T, Li X, Chen Y, Wang J, Karim NA, Zhang Y, Blenis J, Reginato MJ, Henske EP, Yu JJ.
J. of Clinical Investigation Insight; 1(19): e86629, Nov 17, 2016

"O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FoxM1 pathway"
Ferrer CM, Lu TY, Bacigalupa ZA, Katsetos CD, Sinclair DA, and Reginato, MJ
Oncogene, Jun 27 2016 [Epub ahead of print]

"O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling"
Ferrer CM, Sodi VL and Reginato MJ
Journal of Molecular Biology, Jun 22 2016 [Epub ahead of print](add link)

"Progress towards overcoming hypoxia-induced resistance to solid tumor therapy"
Karakashev SV, and Reginato MJ
Cancer Management and Research, 12;7:253-64 Aug 2015

"Sweet Connections: O-GlcNacylation links cancer metabolism and survival"
Ferrer CM, and Reginato MJ
Molecular & Cellular Oncology, Oct 29; 2(1) 2014

"Emerging microtubule targets in glioma therapy"
Katsetos CD, Reginato MJ, Baas PW, D’Agostino L, Legido A, Tuszyn Ski JA, Draberova E, and Draber P
Seminars in Pediatric Neurology; 22(1):49-72, March 2015

"mTOR/c-MYC axis regulates O-GlcNAc transferase (OGT) expression and O-GlcNAcylation in breast cancer"
Sodi VL, Khaku S, Schwab LP, Vocadlo DJ, Seagroves TN and Reginato MJ
Molecular Cancer Research, 13(5):923-33, May 2015
Publication listed in Highlights of This Issue

"Epithelial-to-mesenchymal transition alters interstitial fluid flow-induced signaling in ERBB2-positive breast cancer cells"
Tchafa AM, Ta M,  Reginato MJ and Shieh AC
Molecular Cancer Research, 13(4):755-64, Apr 2015

"Hypoxia/HIF-1a induces lapatinib resistance in ERBB2-positive breast cancer cells via regulation of DUSP2"
Karakashev SV, and Reginato MJ
Oncotarget, 6(4):1967-80, Feb 10, 2015

Book Chapter: "Cancer Metabolism: Cross Talk Between Signaling and O-GlcNAcylation"
Ferrer CM, and Reginato MJ
Cancer Genomics and Proteomics: Methods and Protocols, Methods in Molecular Biology, Vol. 1176 pp 73-88, Springer, Narendra Wajapeyee (Ed.), 2014

"O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of HIF-1 pathway"
Ferrer CM, Lynch TP, Sodi V, Falcone JN, Schwab L, Peacock D, Vocadlo DJ, Seagroves TN, and Reginato MJ 
Molecular Cell; (54(5); 820-831, June 5, 2014

"Sticking to Sugars at the Metastatic Site: Sialyltransferase ST6GalNAc2 Acts as Breast Cancer Metastasis Suppressor"
Ferrer, CM, and Reginato, MJ
Cancer Discovery; March 4(3); 275–7, March 2014

"Activated ERBB2/HER2 licenses sensitivity to apoptosis upon endoplasmic reticulum stress through a PERK-dependent pathway"
Martin-Perez, R, Palacios, C, Yerbes, R, Cano-Gonzales, A, Iglesias-Serret, D, Gil, J, Reginato, MJ and López-Rivas A  
Cancer Research; 74(6): 1766-77, March 15, 2014

"ErbB2, FoxM1, and 14-3-3ζ prime breast cancer cells for invasion in response to ionizing radiation"
Kambach DM, Sodi VL, Lelkes PI, Azizkhan-Clifford J, and Reginato MJ 
Oncogene Jan 30; 33(5):589-98 (2014)

"HINCUTs in Cancer: Hypoxia-induced non-coding ultraconserved transcripts"
Ferdin J, Wu X, Nishida N Nicoloso MS, Shah NM, Devlin C, Ling H, Shimizu M, Kumar K, Cortez MA, Ferracin M, Bi Y, Yang D, Czerniack BA, Zhang W, Schmittgen TD, Voorhoeve MP, Reginato MJ, Negrini M, Davuluri RV, Kunej T, Iva, M, and Calin GA
Cell Death Differ Sep 13 2013 [Epub ahead of print]

"The oncogene HER2/neu (erbB2) requires the Hypoxia-inducible factor HIF-1 for mammary tumor growth and anoikis resistance"
Whelan KA, Schwab L, Karakashev S, Franchetti L, Johannes GJ, Seagrove, TN, and  Reginato MJ
J. Biol Chem May 31; 288(22):15865-77 (2013)

"ERK2 regulated TIMP1 induces hyperproloferation of K-Ras (G12D)-transformed pancreatic ductal cells"
Botta GP, Reichert M, Reginato MJ, Heeg S, Rustgi AK and Lelkes PI
Neoplasia Apr 15 (4): 359-72 (2013)

"Control of FLIPL expression and TRAIL resistance by the extracellular signal regulated kinase (ERK)1/2 pathway in breast epithelial cells"
Yerbes R, López-Rivas A, Reginato MJ, and Palacios C
Cell Death Differ; 19:1908-16, Dec 2012

"Critical role of O-GlcNAc transferase in prostate cancer invasion, angiogenesis, and metastasis"
Lynch TP, Ferrer C, Jackson SR, Shahriari KS, Vosseller K, and Reginato MJ 
J. Biol. Chem. Mar 30; 287: 11070-81 (2012)

Presentations

“On a sugar high: O-GlcNAc regulation of cancer”
Fels Cancer Institute for Personalized Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, Pa. (Nov. 2023)

“Nutrient sensor O-GlcNAcylation: Linking signaling and metabolism in cancer & beyond”
ASBMB Symposium: O-GlcNAc regulation of cellular physiology and pathophysiology, Athens, Ga. (Jul. 2022)

“Role of O-GlcNAcome in breast cancer”
Sidney Kimmel Cancer Center Retreat, Philadelphia, Pa. (Feb. 2022)

“O-GlcNAcylation: Linking metabolism & signaling in cancers”
Keynote Speaker, Cancer Symposium, 6th Latin American Congress of Glycobiology, Mexico City, Mexico (Oct. 2021)

“Nutrient sensor O-GlcNAcylation: Linking signaling and acetate metabolism in brain tumors”
NIH Symposium: The Glycobiology of Cancer (Sep. 2021)

“Signaling and metabolic vulnerabilities in cancer”
Community of Scholars Meeting, Drexel University College of Medicine, Philadelphia Pa. (Mar. 2021)

“O-GlcNAcylation: Linking metabolism & signaling in cancers”
Sydney Kimmel Cancer Center, Translational Cellular Oncology Program Meeting, Thomas Jefferson University, Philadelphia Pa. (Nov. 2020)

“Role of O-GlcNAcome on breast cancer initiating cells”
NCI - The Alliance of Glycobiologists for Cancer Research Annual Meeting, Rockville Md. (Feb. 2020)


Contact Information


Department of Biochemistry & Molecular Biology
245 North 15th Street
Mail Stop 497
Philadelphia, PA 19102
Phone: 215.762.3554
Fax: 215.762.4452